title: How I treat severe combined immunodeficiency.
abstract: Severe combined immunodeficiency (SCID) arises from different genetic defects associated with lymphocyte development and function and presents with severe infections. Allogeneic hematopoietic stem cell transplantation is an extremely effective way of restoring immunity in these individuals. Numerous multicenter studies have identified the factors determining successful outcome, and survival for SCID has shown great improvement. Advances in understanding the genetic basis of disease also mean that we increasingly tailor transplant protocols to the specific SCID form. Wherever possible, we attempt to transplant SCID patients without the use of cytoreductive conditioning, but it is clear that this is only successful for specific SCID forms and, although survival is good, in specific patients there are ongoing humoral defects. We aim to use matched related and unrelated donors (including cord blood) whenever possible and have limited the use of mismatched haploidentical donors. The development of autologous hematopoietic stem cell gene therapy provides another treatment of the X-linked and adenosine deaminase-deficient forms of SCID, and we discuss how we have integrated gene therapy into our treatment strategy. These developments together with the advent of universal newborn screening for SCID should allow for a highly favorable outcome for this otherwise lethal condition.
authors.affiliation: Centre for Immunodeficiency, Molecular Immunology Unit, University College London Institute of Child Health, London, United Kingdom; and.
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.forename: Persis J
authors.initials: PJ
authors.lastname: Amrolia
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
mesh_terms: D000243:Adenosine Deaminase / Q000627:therapeutic use; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D014019:Tissue Donors; D019172:Transplantation Conditioning
chemical_list: D000243:Adenosine Deaminase; C051409:pegademase bovine